Skip to main content
ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #251433

Title: Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

item SAKAI, NOZOMU - University Of Cincinnati
item SHIN, THOMS - University Of Cincinnati
item SCHUSTER, REBECCA - University Of Cincinnati
item BLANCHARD, JOHN - University Of Cincinnati
item LENTSCH, ALEX - University Of Cincinnati
item Johnson, William
item SCHUSCHKE, DALE - University Of Louisville

Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2010
Publication Date: 6/11/2010
Citation: Sakai, N., Shin, T., Schuster, R., Blanchard, J., Lentsch, A.B., Johnson, W.T., Schuschke, D.A. 2010. Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats. Biological Trace Element Research. Available: 10.1007/s12011-010-8743-9.

Interpretive Summary: Although severe dietary copper deficiency is rare in humans, low to marginal copper status can occur from several conditions that cause malabsorption of copper. Several studies with animal models have shown that low copper status promotes inflammation in part through neutrophil activation and accumulation of neutrophil in tissues, but mechanisms thru which marginal copper status influences the inflammatory response following liver injury are not clear. In this study we show that marginal copper status promotes neutrophil accumulation in livers that are injured by blockage of blood flow followed by restoration of blood flow, i.e. ischemic/reperfusion injury. The increased accumulation of neutrophils in the marginally copper deficient rats resulted from increased expression of a cell surface adhesion molecule called ICAM-1 in the injured liver. However, even though neutrophil accumulation was increased in the liver, liver injury was not increased by marginal copper status. This suggests that marginal copper deficiency either impaired neutrophil function in a manner that counteracted deleterious effects resulting from their enhanced accumulation or enhanced mechanisms within the liver that protected against neutrophil activation following ischemic/reperfusion liver injury. These findings indicate that further research is needed to better understand the role of copper status in the inflammatory response associated with liver injury.

Technical Abstract: Copper deficiency can lead to an augmented inflammatory response through effects on both neutrophils and the microvascular endothelium. In the present study, we evaluated the effect of marginal copper deficiency on the inflammatory injury response to hepatic ischemia/reperfusion injury. Male weanling Sprague-Dawley rats were fed purified diets which were either Copper-adequate (6.3 mg/kg) or Copper-marginal (1.62 mg/kg) for 4 weeks prior to undergoing 90 minutes of partial hepatic ischemia followed by 8 hours of reperfusion. Liver injury was assessed by serum levels of alanine aminotransferase and by liver histology. Liver neutrophil accumulation was determined by tissue myeloperoxidase (MPO) content. There was no significant difference in liver injury between copper-adequate and copper-marginal rats. However, liver neutrophil accumulation was significantly increased in copper-marginal rats. These findings were confirmed histologically. Liver expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1) was increased in copper-marginal rats compared to copper-adequate rats. The results suggest that neutrophil accumulation is increased through enhanced ICAM-1 expression in liver of copper-marginal rats after I/R, but that this does not result in increased liver injury.